Advances in Endocrine Therapy for Early and Advanced Breast Cancer

AU Buzdar

Hong Kong J Radiol 2003;6:165-72

Significant advances have been made in the treatment of breast cancer since the link was made between the endocrine system and the disease more than 100 years ago. Tamoxifen was the first successful endocrine therapy although, despite its proven effectiveness, it is associated with side effects such as an increased incidence of endometrial cancer and thromboembolic events, and the development of tamoxifen-resistant tumours is common. Alternative endocrine therapies are now available, including aromatase inhibitors and the oestrogen receptor downregulator fulvestrant. The new third-generation aromatase inhibitors anastrozole and letrozole have both shown superior efficacy to tamoxifen for the first-line treatment of advanced breast cancer. In addition, they have both shown efficacy benefits compared with megestrol acetate for patients failing with tamoxifen, as has the steroidal aromatase inhibitor exemestane. More recently, fulvestrant has been shown to be as effective as anastrozole in the second-line setting and is not significantly different from tamoxifen as first-line treatment for advanced disease. Based on the superior activity compared with tamoxifen in the first-line advanced disease setting, several ongoing trials are investigating the use of third-generation aromatase inhibitors in the adjuvant setting. The Arimidex, Tamoxifen, Alone or in Combination trial found that anastrozole was superior to tamoxifen for several efficacy endpoints, including disease-free survival, time to recurrence, and the incidence of contralateral breast cancer, and showed several important tolerability benefits. An efficacy update confirmed the benefits shown for anastrozole versus tamoxifen, and a safety update showed that anastrozole’s tolerability benefits were maintained in the longer-term. The third-generation aromatase inhibitors offer a choice of endocrine treatment for the first- and second-line treatment of advanced disease, while fulvestrant offers an additional choice for the second-line treatment for patients progressing with prior anti-oestrogens. In the adjuvant setting, anastrozole is currently the only aromatase inhibitor to have proven superiority over tamoxifen so, for the first time, there is now a choice of endocrine therapy for postmenopausal women with early breast cancer.